Therapeutic efficacy of α-lactalbumin coated oleic acid based liposomes against colorectal carcinoma in Caco-2 cells and DMH-treated albino rats

Abstract

Colorectal cancer (CRC) is a malignant tumor recognized as a major cause of morbidity and mortality throughout the world. Therefore, novel liposomes of oleic acid coated with camel α-lactalbumin (α-LA coated liposomes) were developed for their potential antitumor activity against CRC, both in vitro and in DMH-induced CRC-modeled animal. In vitro results indicated the high safety of α-LA coated liposomes towards normal human cells with potent antitumor activity against Caco-2 cells at an IC₅₀ value of 57.01 ± 3.55 µM with selectivity index of 6.92 ± 0.48. This antitumor activity has been attributed to induction of the apoptotic mechanism, as demonstrated by nuclear condensation and arrest of Caco-2 cells in sub-G1 populations. α-LA coated liposomes also revealed a significant up-regulation of the p53 gene combined with a down-regulation of the Bcl2 gene. Moreover, in vivo results revealed that treatment of induced-CRC modeled animals with α-LA coated liposomes for six weeks markedly improved the CRC-disorders; this was achieved from the significant reduction in the values of AFP, CEA, CA19.9, TNF-α, IL-1β, MDA, and NO coupled with remarkable rise in SOD, GPx, GSH, CAT, and CD4+ levels. The histopathological findings asserted the therapeutic potential of α-LA coated liposomes in the treatment of CRC. Therefore, the present results proved the antitumor activity of α-LA coated liposomes against CRC through the restoration of impaired oxidative stress, improved immune response, and reduced inflammation.

Communicated by Ramaswamy H. Sarma

Keywords:

• Colorectal carcinoma
• α-lactalbumin
• oleic acid
• liposome

Author contributions

E.M.E.-F.: conceptualization, investigation, formal analysis, experimental details, writing-review and editing the manuscript. H.E.-G.: investigation, formal analysis, experimental details, writing-review and editing the manuscript. M.M.A.-S.: investigation, formal analysis, experimental details, writing-review and editing the manuscript. K.G.A.-W: investigation, formal analysis, experimental details, writing-review and editing the manuscript. D.G.E.-S.: methodology, writing-review & editing. M.A.: methodology, investigation, formal analysis, experimental details, writing-review and editing the manuscript. All authors have read and agreed to the published version of the manuscript.

Availability of data and materials

All the necessary data used to support the results of this study are included in the manuscript.

Consent for publication

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval and consent to participate

All methods were performed in accordance with the relevant guidelines and regulations, and the experiments done on animals are in accordance with arrive guidelines. The experimental design was accepted by the local research ethical committee (REC) of experimental animal use at the National Research Centre, Cairo, Egypt by applying the principles of replacement, reduction and refinement (the 3Rs).

Additional information

Funding

The study was funded by Academy of Scientific Research & Technology (National Program for Research & Innovation in Health and Biomedical Sciences (PRISM_ 5126) program, Call no. 2/2019/ASRT-Health).